As shown in Figure 4, DCT release from NPs at pH 7.4 was continued for 10 days. Cho HJ, Yoon HY, Koo H, et al. Various nanovehicles, such as liposomes, NPs, and micelles, have been developed and evaluated for DCT delivery to improve delivery efficiency and attenuate unwanted effects.14–16. 1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea, 2Division of Health Sciences, Dongseo University, Busan, Republic of Korea, 3College of Pharmacy, Kangwon National University, Chuncheon, Republic of Korea. Blank NPs did not induce any serious cytotoxicity in PC-3 cells. This research was supported by the National Research Foundation of Korea funded by the Korean government (MSIP) (2009-0083533 and NRF-2012R1A1A1038944). The change in the particle size and size distribution of developed nanoparticulate formulations in 50% (v/v) FBS solution was monitored for 24 hours. Among commercially available block copolymers, poly (styrene)-b-poly (acrylic acid) (PS-b-PAA) may exhibit similar properties because the PS block has good potential for LC anchoring owing to its hydrophobicity. Paclitaxel (PTX) was purchased from Samyang Genex Corporation (Daejeon, Korea). Synthesis of poly(methyl methacrylate)-b-polystyrene with high molecular weight by DPE seeded emulsion polymerization and its application in proton exchange membrane. Toxicity of sulfothreenaphtilenfurane. Basis for revised IDLH: The revised IDLH for styrene is 700 ppm based on acute inhalation toxicity data in humans [AIHA 1959; Stewart et al. Poly(vinyl alcohol) (PVA), 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI), 4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid (HEPES) solution, and sodium bicarbonate (NaHCO3) solution were obtained from Sigma-Aldrich Co. (St Louis, MO, USA). In fact, the thermogram obtained after annealing the blend at 200 °C does not show any clear transition indicating the onset of the merging of the two T g 's (curve b). Male Sprague-Dawley (SD) rats, weighing 250±5 g, were purchased from Orient Bio Inc. (Sungnam, Korea) to study in vivo pharmacokinetics. The centrifuging and resuspending processes were repeated three times to remove PVA. Bull., 1985, (065), p. 25]. Both PS and PDLLA, or their derivatives, have been widely used for biomedical applications, including drug delivery systems.8,18–20 In our previous reports, NPs based on biocompatible polymers were prepared and exhibited improved systemic exposure of the drug, in vivo anti-tumor efficacy, and cancer diagnosis.4,21–23 As a new polymer for drug delivery, PS-PDLLA was used for the fabrication of NPs to deliver DCT. Serum biochemistry parameters after intravenous injection of drug-unloaded NPs into the mouse. DCT concentration was determined using high-performance liquid chromatography (HPLC), equipped with a pump (Waters 1525; Waters Co., Milford, MA, USA), an automatic injector (Waters 717 plus), and dual λ absorbance detector (Waters 2487). After the incubation period, the medium was replaced with MTS-based CellTiter 96 Aqueous One Solution Cell Proliferation Assay Reagent (Promega Corp., Fitchburg, WI, USA) and incubated for 4 hours at 37°C according to the manufacturer’s protocol. However, toxicity and other factors have hindered their clinical application, despite their considerable in vivo performance in animal models. Cellular uptake and distribution of the constructed NPs containing a hydrophobic fluorescent dye was monitored by confocal laser scanning microscopy (CLSM) for 24 hours. The lower limit of quantification (LLOQ) of DCT was 1 ng/mL, and precision and accuracy were within the acceptable range. The detection wavelength, flow rate, and injection volume were 230 nm, 1.0 mL per minute, and 20 μL, respectively. Styrene is an injection mold process, injecting polystyrene into the stampers, the labels were glued on afterward. All mice were reared in a light-controlled room at 22°C±2°C and 55%±5% relative humidity (Animal Center for Pharmaceutical Research, College of Pharmacy, Seoul National University, Seoul, Korea). Spencer HC, Irish DD, Adams EM, Rowe VK [1942]. Breathing high levels of styrene may cause changes in color vision, tiredness, feeling drunk, slowed reaction time, concentration problems, or balance problems. The content of DiI in freeze-dried NPs was determined using an EMax Precision Microplate Reader at 560 nm by disrupting the NPs with DMSO. A sustained drug release pattern can improve systemic exposure of the drug after intravenous injection. Styrene can be found in air, soil, and water after release from the manufacture, use, and disposal of styrene-based products. Moscow, Russia: Centre of International Projects, GKNT, p. 106. Tong R, Chiang HH, Kohane DS. Blank NPs, at a dose of 25 mg/kg, were intravenously injected into mice daily for 1 week, after which several blood biochemistry parameters were obtained as presented in Table 2. Basis for original (SCP) IDLH: The chosen IDLH is based on the statement by Patty [1963] that rats and guinea pigs exposed to 5,000 ppm become unconscious within 1 hour [Spencer et al. Ekkapongpisit M, Giovia A, Follo C, Caputo G, Isidoro C. Biocompatibility, endocytosis, and intracellular trafficking of mesoporous silica and polystyrene nanoparticles in ovarian cancer cells: effects of size and surface charge groups. Understanding the nanoparticle-protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles. Water and soil: Styrene evaporates from shallow soils and surface water. Short-term exposure guidelines: None developed. The released amounts of DCT were determined by the HPLC-ultraviolet (UV) method, as described in the previous section. Abbreviations: FT-IR, Fourier transform infrared; NMR, nuclear magnetic resonance; PS-PDLLA, poly(styrene)-b-poly(DL-lactide). Understanding and controlling the morphology of styrene–isoprene side-group liquid crystalline diblock copolymers C.O. We developed NPs based on a PS-PDLLA copolymer for delivery of DCT via intravenous injection. The obtained DCT-loaded PS-PDLLA NPs were freeze-dried and stored at −70°C (DF8517; Ilshin Laboratory Co., Ltd., Seoul, Korea) for further experiments. In a pharmacokinetic study of DCT in rats, in vivo clearance of PS-PDLLA/DCT NPs decreased while the half-life in blood increased compared to the Taxotere-treated group (P<0.05). Each point indicates the mean ± SD (n≥3). 1968]. The compound evaporates easily and has a sweet smell, although high concentrations have a less pleasant odor. We are experimenting with display styles that make it easier to read articles in PMC. Biocompatibility of PS-PDLLA can be estimated from the biomedical application of each polymer component as reported.27,31 The result of the cytotoxicity test supports the feasibility of PS-PDLLA NPs as a safe drug delivery vehicle. 1989 OSHA PEL: 50 ppm (215 mg/m 3) TWA, 100 ppm (425 mg/m 3) STEL 1993-1994 ACGIH TLV: 50 ppm (213 mg/m 3) TWA, 100 ppm (426 mg/m 3) CEILING [skin]. Chitosan oligosaccharide-arachidic acid-based nanoparticles for anti-cancer drug delivery. Lung-specific delivery of paclitaxel by chitosan-modified PLGA nanoparticles via transient formation of microaggregates. Tween 80 was obtained from Tokyo Chemical Industry Co., Ltd. (Tokyo, Japan). It was expected that the ester linkage in the PDLLA backbone could be degraded via esterase-catalyzed hydrolysis in biological fluids.24 With the degradation of the PDLLA segment, NPs based on PS-PDLLA copolymer could be disassembled to release incorporated hydrophobic drug. In vivo toxicity of blank PS-PDLLA NPs was assessed in a mouse model, based principally on serum biochemical analysis. Furthermore, improved inhibition of cancer cell growth could lead to enhanced in vivo anti-tumor efficacy, based on the stability of the developed NPs in serum (Figure 3). This temperature may therefore be taken as the cloud temperature (T p) for this blend. The analytical data were processed using the MassHunter Workstation Software Quantitative Analysis (vB.05.00; Agilent Technologies). The weight ratio between PS-PDLLA and DCT was 10:1 in the PS-PDLLA/DCT NPs group. Treatment of androgen-independent prostate cancer using antimicrotubule agents docetaxel and estramustine in combination: an experimental study. Polyethylene glycol-conjugated hyaluronic acid-ceramide self-assembled nanoparticles for targeted delivery of doxorubicin. Styrene monomer. DiI, as a hydrophobic fluorescent dye, was incorporated into the nanovesicles instead of DCT for monitoring the intracellular movement of NPs for 24 hours in PC-3 cells. Description of … The PS-PDLLA was purchased from PolySciTech, a division of Akina, Inc. (West Lafayette, IN, USA). In DCT-loaded NPs with a 5:1 polymer:drug weight ratio, 77.06%±9.76% of DCT was released from NPs after 10 days. Blood samples (−300 μL) were collected from the femoral artery at 1, 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes after injection, followed by replenishment with a 0.9% sodium chloride injectable solution containing heparin (20 U/mL) at each time point to prevent blood clotting. Diverse approaches for cancer therapy and diagnosis continue to be pursued.1–3 Among the various formulation types, intravenous administration is the primary choice for cancer treatment, and several injectable formulations for anticancer drug delivery have recently been developed.4–7 In most of these cases, improving aqueous solubility and tumor targeting of anticancer agents have been the primary objectives in the formulation development. Chena, G. Maob, C.K. The retention times of DCT and PTX were 4.8 and 4.9 minutes, respectively. *Please select more than one item to compare Data are presented as means ± SD (n=5). This includes data values and the controlled vocabularies that house them. Polymer Plastics Company, LC 550 Mallory Way Carson City, Nevada 89701 (775) 283-4400 info@polymerplastics.com . Notes: PC-3 cell viability (%) after 24, 48, and 72 hours was measured using an MTS-based assay. Notes: Taxotere® (Sanofi S.A., Paris, France) and PS-PDLLA/DCT NPs at 1 nM, 10 nM, and 100 nM DCT were incubated for (A) 48 and (B) 72 hours. Styrene, liquid hydrocarbon that is important chiefly for its marked tendency to undergo polymerization (a process in which individual molecules are linked to produce extremely large, multiple-unit molecules). Blood-stable, tumor-adaptable disulfide bonded mPEG-(Cys)4-PDLLA micelles for chemotherapy. In vivo pharmacokinetic parameters of DCT in rats after intravenous injection at a dose of 1 mg/kg. Cellular uptake and the distribution pattern of the developed NPs were observed by CLSM (Figure 6). EPA-454/R-93-011 EPA Contract No. In vitro-in vivo translation of lipid nanoparticles for hepatocellular siRNA delivery. Arvizo RR, Saha S, Wang E, Robertson JD, Bhattacharya R, Mukherjee P. Inhibition of tumor growth and metastasis by a self-therapeutic nanoparticle. Nevertheless, only a few among those developed have been approved for clinical applications due to toxicity of the materials and insufficient biodistribution of the nanovehicles to the tumors. In vivo pharmacokinetic study of DCT in rats. Aliquots (50 μL) of the plasma samples were spiked with PTX as an internal standard in acetonitrile (10 μL volume, 1 μg/mL concentration), and mixed with acetonitrile (90 μL) for deproteinization. Photoswitchable nanoparticles for in vivo cancer chemotherapy. All animal experiments were approved by the Animal Care and Use Committee of the College of Pharmacy, Seoul National University. Hearing loss has been observed in animals exposed to very high concentrations of styrene. The emulsion was sonicated for 20 minutes using a probe sonicator (VC-750; Sonics & Materials, Inc., Newtown, CT, USA). New York, NY: Interscience Publishers, Inc., p. 1230. 2nd rev. The supernatant was transferred to the vial and a 5 μL aliquot injected onto a reverse phase C18 column (Poroshell 120 EC-C18, 50×4.6 mm, 2.7 μm; Agilent Technologies, Santa Clara, CA, USA). Taxotere was obtained from Sanofi S.A. Docetaxel (DCT) was acquired from LC Laboratories (Woburn, MA, USA). Saving Lives, Protecting People, The National Institute for Occupational Safety and Health (NIOSH), National Institute for Occupational Safety and Health, Immediately Dangerous To Life or Health (IDLH) Values, U.S. Department of Health & Human Services. Vol. Although the PS-PDLLA copolymer does not include a tumor-targeting moiety, NPs based on the PS-PDLLA copolymer were expected to be efficiently taken up into the cells via endocytosis. In several reports,40–42 polymeric NPs containing DCT were fabricated; improved in vivo pharmacokinetic properties were observed compared to DCT solution or commercial formulations. http://creativecommons.org/licenses/by-nc/3.0/. PC-3 cells were seeded in four-chamber culture slides (BD Biosciences, San Jose, CA, USA) at a density of 1.0×105 cells/well and incubated for 24 hours at 37°C. Industrial hygiene and toxicology. Phosphate-buffered saline (PBS) was purchased from Biosesang (Seongnam, Korea). *P<0.05 compared to the Taxotere group. 4. Air: Styrene is quickly broken down in the air, usually within 1-2 days. II. The fluorescence intensity was stronger at 24 hours compared to the 2- and 4-hour incubated groups. The femoral artery and vein were cannulated with Intramedic™ Polyethylene Tubing (PE-50; Becton, Dickinson & Co., Franklin Lakes, NJ, USA) under anesthesia with Zoletil® (Virbac S. A., Carros, France) at a dose of 50 mg/kg via intramuscular injection. Wang W, Zhang H, Geng W, et al. Characterization of DCT-loaded PS-PDLLA NPs. Using TEM and SAXS, microdomain structures of cylinders of poly (styrene), cylinders of poly (isoprene-LC) as … There was no indication of a concern for chronic toxicity based on these studies. Blood samples (0.8 mL) were then collected by cardiac puncture and aliquots of plasma were obtained by centrifuging at 3,000 rpm for 20 minutes. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Anti-tumor efficacy of DCT-loaded PS-PDLLA NPs was evaluated in PC-3 cells (Figure 7). Walkey CD, Olsen JB, Guo H, Emili A, Chan WC. Abbreviations: DCT, docetaxel; NP, nanoparticle; PS-PDLLA, poly(styrene)-b-poly(DL-lactide). At all DCT concentration (1, 10 and 100 nM) and incubation time (48 and 72 hours) groups, the cell viability (%) of the PS-PDLLA/DCT NP-treated group was lower than that of the Taxotere group (P<0.05). Styrene (C₆H₅CH=CH₂) is a colorless liquid that evaporates easily and has a sweet smell. Thomas C, Rawat A, Hope-Weeks L, Ahsan F. Aerosolized PLA and PLGA nanoparticles enhance humoral, mucosal and cytokine responses to hepatitis B vaccine. NPs with a 10:1 polymer:drug weight ratio exhibited a sustained drug release profile and thus were used in subsequent studies. The particle size was consistently maintained in serum for 24 hours and a sustained drug release pattern was observed for 10 days in the tested formulations. Cellular localization of DiI-loaded NPs was observed as a red color by CLSM (LSM 710; Carl Zeiss). Proteins can bind to the surface of polymeric NPs after intravenous injection of NPs, forming a protein corona.28 Diverse proteins in biological fluids can participate in the formation of protein corona, acting as opsonins related to cellular uptake by a mononuclear phagocyte system (MPS).29 Thus, the interaction between proteins and a polymeric NP surface can modulate the pharmacokinetic properties of the drug and the fate of NPs.30 Stability testing in serum (Figure 3) indicated that DCT-loaded NPs could reach the tumor region without aggregation or precipitation in the blood stream and rapid clearance by the reticuloendothelial system. Cho HJ, Yoon HY, Koo H, et al. Mean diameter of the developed NPs in 50% FBS. This includes data values and the pharmacokinetics of DCT investigated the lower cell viability of the developed blank exhibited. The 2- and 4-hour incubated groups Committee of the commercial formulation, Taxotere RD50! 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